Cannabis intoxication is known to produce psychotic symptoms such as delusions, and disorganized thoughts resembling schizophrenia. In addition, epidemiological data supports a correlation between cannabis use and subsequent development and/or exacerbation of schizophrenia in humans. Schizophrenia is known to inhibit the activity of prefrontal-thalamic-cerebellar network in humans, and has led to the cognitive dysmetria hypothesis of schizophrenia. This posits that a primary dysfunction in the prefrontal-thalamic-cerebellar network underlies the broad range of schizophrenic symptomatology. We will utilize functional magnetic resonance imaging, Fos immunohistochemistry and mass spectroscopy to explore the biological mechanisms by which cannabinoids may inhibit prefrontal-thalamic-cerebellar networks in animals with the aim of further understanding the biological basis for the high correlation between cannabis use and schizophrenia. In addition, we plan to evaluate the role of the endogenous cannabinergic system in the regulation of the prefrontal-thalamic-cerebellar network. We hope that successful completion of these studies will provide enhanced understanding of both the endocannabinoid system and its possible contribution to the pathophysiology of schizophrenia.